tbuckley/cabot-search huggingface dataset:
HRSA Study: US Abortions Decreased 14% During COVID-19
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels
Authors: Brandon A. Mahal, Lucia Kwak, Wanling Xie, James A. Eastham, Nicholas D. James, Howard M. Sandler, Felix Y. Feng, Meryem Brihoum, Karim Fizazi, Christopher Sweeney, Praful Ravi, Anthony V. D’Amico
Journal: JAMA Network Open (2023)

Importance Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; &amp;amp;lt;4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm. Objective To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer–specific mortality (PCSM) and all-cause mortality (ACM). Data Sources PubMed search from 2000 to 2022. Study Selection Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel. Data Extraction and Synthesis Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022. Main Outcomes and Measures Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months). Results From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86]). Conclusions and Relevance Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.
Trial Confirms Antidepressant Improves IBS in Primary Care
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Slow cycling and durable Flt3+ progenitors contribute to hematopoiesis under native conditions
Authors: Michael Solomon, Baobao Song, Vinothini Govindarajah, Samantha Good, Ashok Arasu, E. Broderick Hinton, Kairavee Thakkar, James Bartram, Marie-Dominique Filippi, Jose A. Cancelas, Nathan Salomonis, H. Leighton Grimes, Damien Reynaud
Journal: The Journal of Experimental Medicine (2023)

The dynamics of the hematopoietic flux responsible for blood cell production in native conditions remains a matter of debate. Using CITE-seq analyses, we uncovered a distinct progenitor population that displays a cell cycle gene signature similar to the one found in quiescent hematopoietic stem cells. We further determined that the CD62L marker can be used to phenotypically enrich this population in the Flt3+ multipotent progenitor (MPP4) compartment. Functional in vitro and in vivo analyses validated the heterogeneity of the MPP4 compartment and established the quiescent/slow-cycling properties of the CD62L- MPP4 cells. Furthermore, studies under native conditions revealed a novel hierarchical organization of the MPP compartments in which quiescent/slow-cycling MPP4 cells sustain a prolonged hematopoietic activity at steady-state while giving rise to other lineage-biased MPP populations. Altogether, our data characterize a durable and productive quiescent/slow-cycling hematopoietic intermediary within the MPP4 compartment and highlight early paths of progenitor differentiation during unperturbed hematopoiesis.
Authors' Reply: Integer Cystatin C Values: Impact on Discordance Group Assignment and Accuracy of GFR-Estimating Equations
Authors: Edouard L. Fu, Andrew S. Levey, Lesley A. Inker, Juan-Jesus Carrero
Journal: Journal of the American Society of Nephrology (2023)

We thank Groothof et al.1 for their letter and the opportunity to clarify certain aspects of our analysis.2 In our calculation of eGFR based on creatinine (eGFRcr), eGFR based on cystatin C (eGFRcys), and eGFRcr-cys, we followed current recommendations for reporting cystatin C (using two decimals for values in mg/L) and for serum creatinine (using two decimals for values in mg/dl and integers for values in micromole/L).3,4 Thus, we did not round cystatin C values to the nearest integer before calculations as asserted by Groothof et al. In our baseline table, we rounded cystatin C to the nearest integer; here, we present them using 2 decimals for the interested reader: 1.28 (0.97 to 1.80) mg/L in the overall population, 1.57 (1.23 to 2.12) mg/L for eGFRcys<eGFRcr, 1.01 (0.85 to 1.37) mg/L for eGFRcys≈eGFRcr, and 0.96 (0.80–1.96) mg/L for eGFRcys>eGFRcr. We did not implement a stratified bootstrap but performed bootstrapping followed by stratification by discordance group. Reanalysis using a stratified bootstrap leads to virtually identical results: For the eGFRcys>eGFRcr discordance group, median biases (95% confidence interval [CI]) using a stratified bootstrap are −4.5 (−5.3 to −3.8) ml/min per 1.73 m2 for eGFRcr, 8.4 (7.3 to 10.0) for eGFRcys, and 1.8 (1.1 to 2.5) for eGFRcr-cys. For the eGFRcys<eGFRcr discordance group, median biases (95% CI) using a stratified bootstrap are 15.0 (14.5 to 15.5) ml/min per 1.73 m2 for eGFRcr, −8.6 (−9.0 to −8.3) for eGFRcys, and 0.7 (0.5 to 1.0) for eGFRcr-cys. Similar to Groothof et al., we now also reanalyzed our data by rounding cystatin C values to one decimal or the nearest integer before calculating eGFR. Rounding cystatin C values to one decimal or the nearest integer would result in sample sizes of 736 and 1150, respectively, in the eGFRcys>eGFRcr discordance group (compared with 713 in our main analysis that used two decimals). When rounding cystatin C to one decimal before eGFR calculation, median biases (95% CI) in the eGFRcys>eGFRcr discordance group would be −4.4 (−5.3 to −3.8) ml/min per 1.73 m2 for eGFRcr, 9.5 (7.9 to 11.2) for eGFRcys, and 2.0 (1.5 to 2.8) for eGFRcr-cys. For the eGFRcys<eGFRcr group, median biases would be 15.0 (14.5 to 15.5), −8.7 (−9.0 to −8.3), and 0.7 (0.4 to 1.0), respectively. When rounding cystatin C to the nearest integer, median biases (95% CI) would be −1.0 (−1.3 to −0.5) for eGFRcr, 18.4 (17.4 to 19.3) for eGFRcys, and 10.1 (9.2 to 11.0) for eGFRcr-cys. For the eGFRcys<eGFRcr group, median biases would be 13.1 (12.6 to 13.6), −11.2 (−11.8 to −10.8), and −1.6 (−1.9 to −1.2), respectively. In conclusion, we agree with Groothof et al. that researchers should use two decimals for cystatin C values in mg/L before calculating eGFR.
Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes
Authors: Emily K. Sims, Abhishek Kulkarni, Audrey Hull, Stephanie E. Woerner, Susanne Cabrera, Lucy D. Mastrandrea, Batoul Hammoud, Soumyadeep Sarkar, Ernesto S. Nakayasu, Teresa L. Mastracci, Susan M. Perkins, Fangqian Ouyang, Bobbie-Jo Webb-Robertson, Jacob R. Enriquez, Sarah A. Tersey, Carmella Evans-Molina, S. Alice Long, Lori Blanchfield, Eugene W. Gerner, Raghavendra G. Mirmira, Linda A. DiMeglio
Journal: Cell Reports Medicine (2023)

In preclinical models, α-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, delays the onset of type 1 diabetes (T1D) by reducing β cell stress. However, the mechanism of DFMO action and its human tolerability remain unclear. In this study, we show that mice with β cell ODC deletion are protected against toxin-induced diabetes, suggesting a cell-autonomous role of ODC during β cell stress. In a randomized controlled trial (ClinicalTrials.gov: NCT02384889) involving 41 recent-onset T1D subjects (3:1 drug:placebo) over a 3-month treatment period with a 3-month follow-up, DFMO (125–1,000 mg/m2) is shown to meet its primary outcome of safety and tolerability. DFMO dose-dependently reduces urinary putrescine levels and, at higher doses, preserves C-peptide area under the curve without apparent immunomodulation. Transcriptomics and proteomics of DFMO-treated human islets exposed to cytokine stress reveal alterations in mRNA translation, nascent protein transport, and protein secretion. These findings suggest that DFMO may preserve β cell function in T1D through islet cell-autonomous effects.
Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer
Authors: Joao V Alessi, Adam Price, Allison L Richards, Biagio Ricciuti, Xinan Wang, Arielle Elkrief, Federica Pecci, Alessandro Di Federico, Malini M Gandhi, Emily S Lebow, Patricia Mae G Santos, Maria Thor, Andreas Rimner, Adam J Schoenfeld, Jamie E Chaft, Bruce E Johnson, Daniel R Gomez, Mark M Awad, Narek Shaverdian
Journal: Journal for ImmunoTherapy of Cancer (2023)

There is a need to identify predictive biomarkers to guide treatment strategies in stage III non-small cell lung cancer (NSCLCs). In this multi-institutional cohort of 197 patients with stage III NSCLC treated with concurrent chemoradiation (cCRT) and durvalumab consolidation, we identify that low tumor aneuploidy is independently associated with prolonged progression-free survival (HR 0.63; p=0.03) and overall survival (HR 0.50; p=0.03). Tumors with high aneuploidy had a significantly greater incidence of distant metastasis and shorter median distant-metastasis free survival (p=0.04 and p=0.048, respectively), but aneuploidy level did not associate with local-regional outcomes. Multiplexed immunofluorescence analysis in a cohort of NSCLC found increased intratumoral CD8-positive, PD-1-positive cells, double-positive PD-1 CD8 cells, and FOXP3-positive T-cell in low aneuploid tumors. Additionally, in a cohort of 101 patients treated with cCRT alone, tumor aneuploidy did not associate with disease outcomes. These data support the need for upfront treatment intensification strategies in stage III NSCLC patients with high aneuploid tumors and suggest that tumor aneuploidy is a promising predictive biomarker.
Epithelial-mesenchymal transition in age-associated thymic involution: Mechanisms and therapeutic implications
Authors: Jiali Yang, Juan Liu, Jiayu Liang, Fan Li, Wenwen Wang, Huan Chen, Xiang Xie
Journal: Ageing Research Reviews (2023)

The thymus is a critical immune organ with endocrine and immune functions that plays important roles in the physiological and pathological processes of the body. However, with aging, the thymus undergoes degenerative changes leading to decreased production and output of naive T cells and the secretion of thymic hormones and related cytokines, thereby promoting the occurrence and development of various age-associated diseases. Therefore, identifying essential processes that regulate age-associated thymic involution is crucial for long-term control of thymic involution and age-associated disease progression. Epithelial-mesenchymal transition (EMT) is a well-established process involved in organ aging and functional impairment through tissue fibrosis in several organs, such as the heart and kidney. In the thymus, EMT promotes fibrosis and potentially adipogenesis, leading to thymic involution. This review focuses on the factors involved in thymic involution, including oxidative stress, inflammation, and hormones, from the perspective of EMT. Furthermore, current interventions for reversing age-associated thymic involution by targeting EMT-associated processes are summarized. Understanding the key mechanisms of thymic involution through EMT as an entry point may promote the development of new therapies and clinical agents to reverse thymic involution and age-associated disease.
Improved efficacy of FKRP AAV gene therapy by combination with ribitol treatment for LGMD2I
Authors: Marcela P. Cataldi, Charles H. Vannoy, Anthony Blaeser, Jason D. Tucker, Victoria Leroy, Raegan Rawls, Jessalyn Killilee, Molly C. Holbrook, Qi Long Lu
Journal: Molecular Therapy (2023)
Untargeted metabolomic profiling in children identifies novel pathways in asthma and atopy
Authors: Stéphanie Lejeune, Abhinav Kaushik, Ella S. Parsons, Sharon Chinthrajah, Michael Snyder, Manisha Desai, Monali Manohar, Mary Prunicki, Kévin Contrepois, Philippe Gosset, Antoine Deschildre, Kari Nadeau
Journal: Journal of Allergy and Clinical Immunology (2023)
High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice
Authors: Xiaojuan Chao, Mengwei Niu, Shaogui Wang, Xiaowen Ma, Xiao Yang, Hua Sun, Xujia Hu, Hua Wang, Li Zhang, Ruili Huang, Menghang Xia, Andrea Ballabio, Hartmut Jaeschke, Hong-Min Ni, Wen-Xing Ding
Journal: Acta Pharmaceutica Sinica B (2023)

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.
Frailty and sarcopenia: A bibliometric analysis of their association and potential targets for intervention
Authors: Lian Ye, Rui Liang, Xiaolei Liu, Jun Li, Jirong Yue, Xinjun Zhang
Journal: Ageing Research Reviews (2023)

Frailty and sarcopenia are age-related diseases, and exhibit a concomitant relationship, as they share many common clinical features and etiological factors. Transitions within frailty status would be influenced by the presence of sarcopenia. Investigating their association to devise efficacious intervention and management strategies for geriatric patients is imperative, given their potentially unfavorable outcomes. In this study, the literature on sarcopenia and frailty was screened in the Web of Science core collection database over the past 30 years to ascertain the link between them through bibliometric analysis and the exploration of disease-related molecular pathways within the GeneCards and OMIM databases was conducted. Per inclusion and exclusion criteria, 3889 literature sources were selected for subsequent analysis. Keywords, including "cirrhosis" and "postoperative complications," represent the current and potential future research trends and focal points in this field. Moreover, 63 common potential targets between the two diseases were identified. Their pathogenesis involved cellular aging and endocrine metabolism regulation pathways, including AMPK, cell senescence, and the endocrine resistance pathway. This study identified an intimate correlation between frailty and sarcopenia in pathogenesis, prevention, and treatment measures, establishing a foundation for exploring shared prevention and treatment strategies for these two disorders.
CenTime: Event-conditional modelling of censoring in survival analysis
Authors: Ahmed H. Shahin, An Zhao, Alexander C. Whitehead, Daniel C. Alexander, Joseph Jacob, David Barber
Journal: Medical Image Analysis (2023)

Survival analysis is a valuable tool for estimating the time until specific events, such as death or cancer recurrence, based on baseline observations. This is particularly useful in healthcare to prognostically predict clinically important events based on patient data. However, existing approaches often have limitations; some focus only on ranking patients by survivability, neglecting to estimate the actual event time, while others treat the problem as a classification task, ignoring the inherent time-ordered structure of the events. Additionally, the effective utilisation of censored samples-data points where the event time is unknown- is essential for enhancing the model's predictive accuracy. In this paper, we introduce CenTime, a novel approach to survival analysis that directly estimates the time to event. Our method features an innovative event-conditional censoring mechanism that performs robustly even when uncensored data is scarce. We demonstrate that our approach forms a consistent estimator for the event model parameters, even in the absence of uncensored data. Furthermore, CenTime is easily integrated with deep learning models with no restrictions on batch size or the number of uncensored samples. We compare our approach to standard survival analysis methods, including the Cox proportional-hazard model and DeepHit. Our results indicate that CenTime offers state-of-the-art performance in predicting time-to-death while maintaining comparable ranking performance. Our implementation is publicly available at https://github.com/ahmedhshahin/CenTime.
2023 World Heart Federation guidelines for the echocardiographic diagnosis of rheumatic heart disease
Authors: Joselyn Rwebembera, James Marangou, Julius Chacha Mwita, Ana Olga Mocumbi, Cleonice Mota, Emmy Okello, Bruno Nascimento, Lene Thorup, Andrea Beaton, Joseph Kado, Alexander Kaethner, Raman Krishna Kumar, John Lawrenson, Eloi Marijon, Mariana Mirabel, Maria Carmo Pereira Nunes, Daniel Piñeiro, Fausto Pinto, Kate Ralston, Craig Sable, Amy Sanyahumbi, Anita Saxena, Karen Sliwa, Andrew Steer, Satupaitea Viali, Gavin Wheaton, Nigel Wilson, Liesl Zühlke, Bo Reményi
Journal: Nature Reviews Cardiology (2023)
CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress
Authors: Yuanjun Lu, Yau-Tuen Chan, Junyu Wu, Zixin Feng, Hongchao Yuan, Qiucheng Li, Tingyuan Xing, Lin Xu, Cheng Zhang, Hor-Yue Tan, Terence Kin-Wah Lee, Yibin Feng, Ning Wang
Journal: Drug Resistance Updates (2023)

Therapeutic outcome of sorafenib in hepatocellular carcinoma (HCC) is undermined by the development of drug resistance. This study aimed to identify the critical microRNA (miRNA) which is responsible for sorafenib resistance at the genomic level. CRISPR/Cas9 screen followed by gain- and loss-of-function assays both in vitro and in vivo were applied to identify the role of miR-3689a-3p in mediating sorafenib response in HCC. The upstream and downstream molecules of miR-3689a-3p and their mechanism of action were investigated. CRISPR/Cas9 screening identified miR-3689a-3p was the most up-regulated miRNA in sorafenib sensitive HCC. Knockdown of miR-3689a-3p significantly increased sorafenib resistance, while its overexpression sensitized HCC response to sorafenib treatment. Proteomic analysis revealed that the effect of miR-3689a-3p was related to the copper-dependent mitochondrial superoxide dismutase type 1 (SOD1) activity. Mechanistically, miR-3689a-3p targeted the 3′UTR of the intracellular copper chaperone for superoxide dismutase (CCS) and suppressed its expression. As a result, miR-3689a-3p disrupted the intracellular copper trafficking and reduced SOD1-mediated scavenge of mitochondrial oxidative stress that eventually caused HCC cell death in response to sorafenib treatment. CCS overexpression blunted sorafenib response in HCC. Clinically, miR-3689a-3p was down-regulated in HCC and predicted favorable prognosis for HCC patients. Our findings provide comprehensive evidence for miR-3689a-3p as a positive regulator and potential druggable target for improving sorafenib treatment in HCC.